Elucidation of anti-HIV mechanism of sulfated cellobiose-polylysine dendrimers

Three new spherical sulfated cellobiose-polylysine dendrimers of increasing generations bearing negatively charged sulfate groups were prepared by sulfating the corresponding cellobiose-polylysine dendrimers. The first, second, and third-generation derivatives exhibited potent anti-HIV activity with EC50 values of 3.7, 0.6, and 1.5 mu g/mL, respectively, in constant to sulfated oligosaccharides with low anti-HIV activity, while the second generation sulfated dendrimer was the most active. Surface plasmon resonance measurements with poly-L lysine bearing positively charged amino acids as a model of the HIV surface glycoprotein gp120, indicated that the second-generation dendrimer had the lowest dissociation constant (K-D = 1.86 x 10(-12) M). Both the particle size and zeta potential increased in the presence of poly-L-lysine. It was proven that the moderate distance between the terminal sulfated cellobiose units in the second-generation dendrimer favored the high anti-HIV activity, owing to the electrostatic interactions developed due to the cluster effect.